Fibrinogen plays an essential role in platelet aggregation. Following platelet activation, fibrinogen binds to a calcium- dependent complex of platelet membrane glycoproteins (Gp) IIb and IIIa. It has been proposed that fibrinogen, with a dimeric structure and two-fold symmetry, may act as a bridge between two Gp IIb-IIIa complex in adjacent platelets. At least two well- defined sequences in fibrinogen, the gamma-400-411 in the N- terminal part of gamma chain and the Arg-Gly-Asp sequences in the A alpha chain (A alpha 95-97 and/or A alpha 574-576) are shown to interact with platelet Gp IIb-IIIa. We have recently shown that the synthetic peptide B beta 15-42 derived from amino terminal end of B beta chain, inhibits ADP and thrombin-induced platelet aggregation in a dose-dependent manner. Furthermore, in binding studies this peptide inhibits 125I-fibrinogen binding to activated platelets. This peptide is generated in vivo by the combined actions of thrombin and plasmin on fibrin(ogen) and has been detected in peripheral blood. The aims of this proposal are to further define the minimal aminoacid sequence required for this effect, to determine whether the effect of this peptide is mediated through its interaction with Gp IIb-IIIa or with fibrinogen, and to determine the effect of this peptide on the interaction of other adhesive glycoproteins to Gp IIb-IIIa. In addition, fibrinogen lacking B beta 15-42 will be prepared by cleavage with Protease III from Crotalus atrox venom and the effect of this fibrinogen on platelet aggregation will be determined. These studies will elucidate the importance of aminoterminal end of B beta chain in platelet-fibrinogen interactions.